PROJECT SUMMARY As the Human Genome Project (HGP) approached its successful conclusion, NIH was in the process of formulating the Roadmap, which evolved into the Common Fund. At the leading edge of these initiatives was the Biomedical Engineering Research Partnership (BRP), which promoted technology development. For the BRP, Sklar led the development of high throughput flow cytometry, a screening technology which transitioned into the Molecular Libraries Program (MLP), a logical successor to the HGP, to develop small molecule probes for newly discovered genomic targets. For the Common Fund, Illuminating the Druggable Genome (IDG) became the next logical successor to prioritize genomic targets for further investigation. The technology advanced via the BRP by Sklar became a foundation for the collaboration with Oprea resulting in 10 years of participation in the MLP through both pilot and production phases, with Sklar leading both administrative and laboratory efforts and Oprea leading the data science efforts. Toward the end of the MLP, Oprea, Sklar, and Schrer, who had also been part of the MLP since the pilot phase, joined forces for the BARD initiative (2012- 14) and again in Phase I (2015-17) and this Phase II IDG proposal (2018-24). Despite steady progress in developing novel therapeutics and their enormous medical and societal benefits, current drugs target only a small fraction of the human proteome. Even drugs in clinical development and most preclinical drug discovery research ignore a significant portion of the druggable proteome. Through the development, broad dissemination, and use of community scientific resources, the IDG program is focused on advancing research to study human proteins for which publicly available information or active research is currently lacking, in order to catalyze the discovery of novel biology with a particular focus on understudied members of the protein kinase, ion channel, and non-olfactory GPCR families. Our highly-coordinated team from the University of New Mexico and the University of Miami will establish the IDG Resource Dissemination and Outreach Center (RDOC) to facilitate widespread access to consortium- generated data and resources as well as to serve the overall administration of the IDG Consortium and its relationships with external partners. The IDG-RDOC will work with all IDG Consortium investigators to collect and curate information regarding critical tools and reagents being developed by the IDG Consortium and disseminate them through the IDG Portal. Specifically we will: (i) coordinate and support the IDG consortium via a highly experienced administrative team; (ii) facilitate and coordinate external partnerships, outreach, and training related to IDG program activities; and (iii) develop and implement data standards, policies, operations, and tools to collect, curate, identify, and disseminate IDG-generated resources in accordance with (extended) NIH FAIR (Findable, Accessible, Attributable, Interoperable, Reusable, Reproducible) principles. 1